Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Molecular Targets for Therapy

Erucylphosphohomocholine, the first intravenously applicable alkylphosphocholine, is cytotoxic to acute myelogenous leukemia cells through JNK- and PP2A-dependent mechanisms

Leukemia volume 24, pages 687–698 (2010)Cite this article

Subjects

Abstract

Alkylphospholipids and alkylphosphocholines (APCs) are promising antitumor agents, which target the plasma membrane and affect multiple signal transduction networks. We investigated the therapeutic potential of erucylphosphohomocholine (ErPC3), the first intravenously applicable APC, in human acute myelogenous leukemia (AML) cells. ErPC3 was tested on AML cell lines, as well as AML primary cells. At short (6–12 h) incubation times, the drug blocked cells in G2/M phase of the cell cycle, whereas, at longer incubation times, it decreased survival and induced cell death by apoptosis. ErPC3 caused JNK 1/2 activation as well as ERK 1/2 dephosphorylation. Pharmacological inhibition of caspase-3 or a JNK 1/2 inhibitor peptide markedly reduced ErPC3 cytotoxicity. Protein phosphatase 2A downregulation by siRNA opposed ERK 1/2 dephosphorylation and blunted the cytotoxic effect of ErPC3. ErPC3 was cytotoxic to AML primary cells and reduced the clonogenic activity of CD34+ leukemic cells. ErPC3 induced a significant apoptosis in the compartment (CD34+ CD38Low/Neg CD123+) enriched in putative leukemia-initiating cells. This conclusion was supported by ErPC3 cytotoxicity on AML blasts showing high aldehyde dehydrogenase activity and on the side population of AML cell lines and blasts. These findings indicate that ErPC3 might be a promising therapeutic agent for the treatment of AML patients.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Get just this article for as long as you need it

$39.95

Learn more

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6

References

  1. van Blitterswijk WJ, Verheij M . Anticancer alkylphospholipids: mechanisms of action, cellular sensitivity and resistance, and clinical prospects. Curr Pharm Design 2008; 14: 2061–2074.

    Article  CAS  Google Scholar 

  2. Berger MR, Muschiol C, Schmahl D, Eibl HJ . New cytostatics with experimentally different toxic profiles. Cancer Treat Rev 1987; 14: 307–317.

    Article  CAS  PubMed  Google Scholar 

  3. van der Luit AH, Vink SR, Klarenbeek JB, Perrissoud D, Solary E, Verheij M et al. A new class of anticancer alkylphospholipids uses lipid rafts as membrane gateways to induce apoptosis in lymphoma cells. Mol Cancer Ther 2007; 6: 2337–2345.

    Article  CAS  PubMed  Google Scholar 

  4. Gajate C, Mollinedo F . Edelfosine and perifosine induce selective apoptosis in multiple myeloma by recruitment of death receptors and downstream signaling molecules into lipid rafts. Blood 2007; 109: 711–719.

    Article  CAS  PubMed  Google Scholar 

  5. Steelman LS, Abrams SL, Whelan J, Bertrand FE, Ludwig DE, Basecke J et al. Contributions of the Raf/MEK/ERK, PI3K/PTEN/Akt/mTOR and Jak/STAT pathways to leukemia. Leukemia 2008; 22: 686–707.

    Article  CAS  PubMed  Google Scholar 

  6. McCubrey JA, Steelman LS, Abrams SL, Bertrand FE, Ludwig DE, Basecke J et al. Targeting survival cascades induced by activation of Ras/Raf/MEK/ERK, PI3K/PTEN/Akt/mTOR and Jak/STAT pathways for effective leukemia therapy. Leukemia 2008; 22: 708–722.

    Article  CAS  PubMed  Google Scholar 

  7. Vogler WR, Berdel WE, Olson AC, Winton EF, Heffner LT, Gordon DS . Autologous bone marrow transplantation in acute leukemia with marrow purged with alkyl-lysophospholipid. Blood 1992; 80: 1423–1429.

    CAS  PubMed  Google Scholar 

  8. Andreesen R, Modolell M, Weltzien HU, Eibl H, Common HH, Lohr GW et al. Selective destruction of human leukemic cells by alkyl-lysophospholipids. Cancer Res 1978; 38: 3894–3899.

    CAS  PubMed  Google Scholar 

  9. Vogler WR, Olson AC, Okamoto S, Somberg LB, Glasser L . Experimental studies on the role of alkyl lysophospholipids in autologous bone marrow transplantation. Lipids 1987; 22: 919–924.

    Article  CAS  PubMed  Google Scholar 

  10. Eibl H . Miltefosine for visceral leishmaniasis. New Engl J Med 2000; 342: 894–895.

    Article  CAS  PubMed  Google Scholar 

  11. Gills JJ, Dennis PA . Perifosine: update on a novel Akt inhibitor. Curr Oncol Rep 2009; 11: 102–110.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Mitsiades CS, Hideshima T, Chauhan D, McMillin DW, Klippel S, Laubach JP et al. Emerging treatments for multiple myeloma: beyond immunomodulatory drugs and bortezomib. Semin Hematol 2009; 46: 166–175.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Korkaya H, Paulson A, Charafe-Jauffret E, Ginestier C, Brown M, Dutcher J et al. Regulation of mammary stem/progenitor cells by PTEN/Akt/β-catenin signaling. PLoS Biol 2009; 7: e1000121.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Papa V, Tazzari PL, Chiarini F, Cappellini A, Ricci F, Billi AM et al. Proapoptotic activity and chemosensitizing effect of the novel Akt inhibitor perifosine in acute myelogenous leukemia cells. Leukemia 2008; 22: 147–160.

    Article  CAS  PubMed  Google Scholar 

  15. Tazzari PL, Tabellini G, Ricci F, Papa V, Bortul R, Chiarini F et al. Synergistic proapoptotic activity of recombinant TRAIL plus the Akt inhibitor Perifosine in acute myelogenous leukemia cells. Cancer Res 2008; 68: 9394–9403.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Georgieva MC, Konstantinov SM, Topashka-Ancheva M, Berger MR . Combination effects of alkylphosphocholines and gemcitabine in malignant and normal hematopoietic cells. Cancer Lett 2002; 182: 163–174.

    Article  CAS  PubMed  Google Scholar 

  17. Jendrossek V, Erdlenbruch B, Hunold A, Kugler W, Eibl H, Lakomek M . Erucylphosphocholine, a novel antineoplastic ether lipid, blocks growth and induces apoptosis in brain tumor cell lines in vitro. Int J Oncol 1999; 14: 15–22.

    CAS  PubMed  Google Scholar 

  18. Fiegl M, Lindner LH, Juergens M, Eibl H, Hiddemann W, Braess J . Erufosine, a novel alkylphosphocholine, in acute myeloid leukemia: single activity and combination with other antileukemic drugs. Cancer Chemother Pharmacol 2008; 62: 321–329.

    Article  CAS  PubMed  Google Scholar 

  19. Horn S, Bergholz U, Jucker M, McCubrey JA, Trumper L, Stocking C et al. Mutations in the catalytic subunit of class IA PI3K confer leukemogenic potential to hematopoietic cells. Oncogene 2008; 27: 4096–4106.

    Article  CAS  PubMed  Google Scholar 

  20. Fala F, Blalock WL, Tazzari PL, Cappellini A, Chiarini F, Martinelli G et al. Proapoptotic activity and chemosensitizing effect of the novel Akt inhibitor (2S)-1-(1H-Indol-3-yl)-3-[5-(3-methyl-2H-indazol-5-yl)pyridin-3-yl]oxyprop an2-amine (A443654) in T-cell acute lymphoblastic leukemia. Mol Pharmacol 2008; 74: 884–895.

    Article  CAS  PubMed  Google Scholar 

  21. Nyakern M, Tazzari PL, Finelli C, Bosi C, Follo MY, Grafone T et al. Frequent elevation of Akt kinase phosphorylation in blood marrow and peripheral blood mononuclear cells from high-risk myelodysplastic syndrome patients. Leukemia 2006; 20: 230–238.

    Article  CAS  PubMed  Google Scholar 

  22. Follo MY, Finelli C, Bosi C, Martinelli G, Mongiorgi S, Baccarani M et al. PI-PLCβ-1 and activated Akt levels are linked to azacitidine responsiveness in high-risk myelodysplastic syndromes. Leukemia 2008; 22: 198–200.

    Article  CAS  PubMed  Google Scholar 

  23. Follo MY, Finelli C, Mongiorgi S, Clissa C, Bosi C, Martinelli G et al. PKR is activated in MDS patients and its subcellular localization depends on disease severity. Leukemia 2008; 22: 2267–2269.

    Article  CAS  PubMed  Google Scholar 

  24. Silva A, Yunes JA, Cardoso BA, Martins LR, Jotta PY, Abecasis M et al. PTEN posttranslational inactivation and hyperactivation of the PI3K/Akt pathway sustain primary T cell leukemia viability. J Clin Invest 2008; 118: 3762–3774.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Chiarini F, Del Sole M, Mongiorgi S, Gaboardi GC, Cappellini A, Mantovani I et al. The novel Akt inhibitor, perifosine, induces caspase-dependent apoptosis and downregulates P-glycoprotein expression in multidrug-resistant human T-acute leukemia cells by a JNK-dependent mechanism. Leukemia 2008; 22: 1106–1116.

    Article  CAS  PubMed  Google Scholar 

  26. Renner AG, Dos Santos C, Recher C, Bailly C, Creancier L, Kruczynski A et al. Polo-like kinase 1 is overexpressed in acute myeloid leukemia and its inhibition preferentially targets the proliferation of leukemic cells. Blood 2009; 114: 659–662.

    Article  CAS  PubMed  Google Scholar 

  27. Chiarini F, Fala F, Tazzari PL, Ricci F, Astolfi A, Pession A et al. Dual inhibition of class IA phosphatidylinositol 3-kinase and mammalian target of rapamycin as a new therapeutic option for T-cell acute lymphoblastic leukemia. Cancer Res 2009; 69: 3520–3528.

    Article  CAS  PubMed  Google Scholar 

  28. Park S, Chapuis N, Bardet V, Tamburini J, Gallay N, Willems L et al. PI-103, a dual inhibitor of class I A phosphatidylinositide 3-kinase and mTOR, has antileukemic activity in AML. Leukemia 2008; 22: 1698–1706.

    Article  CAS  PubMed  Google Scholar 

  29. Cheung AM, Wan TS, Leung JC, Chan LY, Huang H, Kwong YL et al. Aldehyde dehydrogenase activity in leukemic blasts defines a subgroup of acute myeloid leukemia with adverse prognosis and superior NOD/SCID engrafting potential. Leukemia 2007; 21: 1423–1430.

    Article  CAS  PubMed  Google Scholar 

  30. Riccioni R, Senese M, Diverio D, Riti V, Buffolino S, Mariani G et al. M4 and M5 acute myeloid leukaemias display a high sensitivity to Bortezomib-mediated apoptosis. Br J Haematol 2007; 139: 194–205.

    Article  CAS  PubMed  Google Scholar 

  31. Cabana R, Frolova EG, Kapoor V, Thomas RA, Krishan A, Telford WG . The minimal instrumentation requirements for Hoechst side population analysis: stem cell analysis on low-cost flow cytometry platforms. Stem Cells 2006; 24: 2573–2581.

    Article  PubMed  Google Scholar 

  32. Borsello T, Clarke PG, Hirt L, Vercelli A, Repici M, Schorderet DF et al. A peptide inhibitor of c-Jun N-terminal kinase protects against excitotoxicity and cerebral ischemia. Nat Med 2003; 9: 1180–1186.

    Article  CAS  PubMed  Google Scholar 

  33. Barr RK, Kendrick TS, Bogoyevitch MA . Identification of the critical features of a small peptide inhibitor of JNK activity. J Biol Chem 2002; 277: 10987–10997.

    Article  CAS  PubMed  Google Scholar 

  34. Chen R, Kang VH, Chen J, Shope JC, Torabinejad J, DeWald DB et al. A monoclonal antibody to visualize PtdIns(3,4,5)P(3) in cells. J Histochem Cytochem 2002; 50: 697–708.

    Article  CAS  PubMed  Google Scholar 

  35. Hayakawa M, Kaizawa H, Moritomo H, Koizumi T, Ohishi T, Okada M et al. Synthesis and biological evaluation of 4-morpholino-2-phenylquinazolines and related derivatives as novel PI3 kinase p110α inhibitors. Bioorgan Med Chem 2006; 14: 6847–6858.

    Article  CAS  Google Scholar 

  36. Billottet C, Grandage VL, Gale RE, Quattropani A, Rommel C, Vanhaesebroeck B et al. A selective inhibitor of the p110δ isoform of PI 3-kinase inhibits AML cell proliferation and survival and increases the cytotoxic effects of VP16. Oncogene 2006; 25: 6648–6659.

    Article  CAS  PubMed  Google Scholar 

  37. Kondapaka SB, Singh SS, Dasmahapatra GP, Sausville EA, Roy KK . Perifosine, a novel alkylphospholipid, inhibits protein kinase B activation. Mol Cancer Ther 2003; 2: 1093–1103.

    CAS  PubMed  Google Scholar 

  38. Wang PY, Liu P, Weng J, Sontag E, Anderson RG . A cholesterol-regulated PP2A/HePTP complex with dual specificity ERK1/2 phosphatase activity. EMBO J 2003; 22: 2658–2667.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Kim SH, Markham JA, Weiler IJ, Greenough WT . Aberrant early-phase ERK inactivation impedes neuronal function in fragile X syndrome. Proc Natl Acad Sci USA 2008; 105: 4429–4434.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Chen L, Liu L, Yin J, Luo Y, Huang S . Hydrogen peroxide-induced neuronal apoptosis is associated with inhibition of protein phosphatase 2A and 5, leading to activation of MAPK pathway. Int J Biochem Cell Biol 2009; 41: 1284–1295.

    Article  CAS  PubMed  Google Scholar 

  41. Deng X, Gao F, May WS . Protein phosphatase 2A inactivates Bcl2′s antiapoptotic function by dephosphorylation and up-regulation of Bcl2-p53 binding. Blood 2009; 113: 422–428.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Deng X, Xiao L, Lang W, Gao F, Ruvolo P, May Jr WS . Novel role for JNK as a stress-activated Bcl2 kinase. J Biol Chem 2001; 276: 23681–23688.

    Article  CAS  PubMed  Google Scholar 

  43. Deng X, Ruvolo P, Carr B, May Jr WS . Survival function of ERK1/2 as IL-3-activated, staurosporine-resistant Bcl2 kinases. Proc Natl Acad Sci USA 2000; 97: 1578–1583.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Nishioka C, Ikezoe T, Yang J, Yokoyama A . Inhibition of MEK signaling enhances the ability of cytarabine to induce growth arrest and apoptosis of acute myelogenous leukemia cells. Apoptosis 2009; 14: 1108–1120.

    Article  CAS  PubMed  Google Scholar 

  45. Kumar P, Coltas IK, Kumar B, Chepeha DB, Bradford CR, Polverini PJ . Bcl-2 protects endothelial cells against gamma-radiation via a Raf-MEK-ERK-survivin signaling pathway that is independent of cytochrome c release. Cancer Res 2007; 67: 1193–1202.

    Article  CAS  PubMed  Google Scholar 

  46. Zhang W, Konopleva M, Ruvolo VR, McQueen T, Evans RL, Bornmann WG et al. Sorafenib induces apoptosis of AML cells via Bim-mediated activation of the intrinsic apoptotic pathway. Leukemia 2008; 22: 808–818.

    Article  CAS  PubMed  Google Scholar 

  47. Rambal AA, Panaguiton ZL, Kramer L, Grant S, Harada H . MEK inhibitors potentiate dexamethasone lethality in acute lymphoblastic leukemia cells through the pro-apoptotic molecule BIM. Leukemia 2009; 23: 1744–1754.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Buitrago CG, Pardo VG, de Boland AR, Boland R . Activation of RAF-1 through Ras and protein kinase C alpha mediates 1α,25(OH)2-vitamin D3 regulation of the mitogen-activated protein kinase pathway in muscle cells. J Biol Chem 2003; 278: 2199–2205.

    Article  CAS  PubMed  Google Scholar 

  49. Tsao CC, Nica AF, Kurinna SM, Jiffar T, Mumby M, Ruvolo PP . Mitochondrial protein phosphatase 2A regulates cell death induced by simulated ischemia in kidney NRK-52E cells. Cell Cycle 2007; 6: 2377–2385.

    Article  CAS  PubMed  Google Scholar 

  50. Bardet V, Tamburini J, Ifrah N, Dreyfus F, Mayeux P, Bouscary D et al. Single cell analysis of phosphoinositide 3-kinase/Akt and ERK activation in acute myeloid leukemia by flow cytometry. Haematologica 2006; 91: 757–764.

    CAS  PubMed  Google Scholar 

  51. Misaghian N, Ligresti G, Steelman LS, Bertrand FE, Basecke J, Libra M et al. Targeting the leukemic stem cell: the Holy Grail of leukemia therapy. Leukemia 2009; 23: 25–42.

    Article  CAS  PubMed  Google Scholar 

  52. Pearce DJ, Taussig D, Simpson C, Allen K, Rohatiner AZ, Lister TA et al. Characterization of cells with a high aldehyde dehydrogenase activity from cord blood and acute myeloid leukemia samples. Stem Cells 2005; 23: 752–760.

    Article  CAS  PubMed  Google Scholar 

  53. Hess DA, Meyerrose TE, Wirthlin L, Craft TP, Herrbrich PE, Creer MH et al. Functional characterization of highly purified human hematopoietic repopulating cells isolated according to aldehyde dehydrogenase activity. Blood 2004; 104: 1648–1655.

    Article  CAS  PubMed  Google Scholar 

  54. Mirabelli P, Di Noto R, Lo Pardo C, Morabito P, Abate G, Gorrese M et al. Extended flow cytometry characterization of normal bone marrow progenitor cells by simultaneous detection of aldehyde dehydrogenase and early hematopoietic antigens: implication for erythroid differentiation studies. BMC Physiol 2008; 8: 13.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Shukla S, Sauna ZE, Ambudkar SV . Evidence for the interaction of imatinib at the transport-substrate site(s) of the multidrug-resistance-linked ABC drug transporters ABCB1 (P-glycoprotein) and ABCG2. Leukemia 2008; 22: 445–447.

    Article  CAS  PubMed  Google Scholar 

  56. Bleau AM, Hambardzumyan D, Ozawa T, Fomchenko EI, Huse JT, Brennan CW et al. PTEN/PI3K/Akt pathway regulates the side population phenotype and ABCG2 activity in glioma tumor stem-like cells. Cell Stem Cell 2009; 4: 226–235.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Wulf GG, Wang RY, Kuehnle I, Weidner D, Marini F, Brenner MK et al. A leukemic stem cell with intrinsic drug efflux capacity in acute myeloid leukemia. Blood 2001; 98: 1166–1173.

    Article  CAS  PubMed  Google Scholar 

  58. Ho MM, Ng AV, Lam S, Hung JY . Side population in human lung cancer cell lines and tumors is enriched with stem-like cancer cells. Cancer Res 2007; 67: 4827–4833.

    Article  CAS  PubMed  Google Scholar 

  59. Allen JD, van Loevezijn A, Lakhai JM, van der Valk M, van Tellingen O, Reid G et al. Potent and specific inhibition of the breast cancer resistance protein multidrug transporter in vitro and in mouse intestine by a novel analogue of fumitremorgin C. Mol Cancer Ther 2002; 1: 417–425.

    Article  CAS  PubMed  Google Scholar 

  60. Kugler W, Erdlenbruch B, Otten K, Jendrossek V, Eibl H, Lakomek M . MAP kinase pathways involved in glioblastoma response to erucylphosphocholine. Int J Oncol 2004; 25: 1721–1727.

    CAS  PubMed  Google Scholar 

  61. Gallay N, Dos Santos C, Cuzin L, Bousquet M, Simmonet Gouy V, Chaussade C et al. The level of AKT phosphorylation on threonine 308 but not on serine 473 is associated with high-risk cytogenetics and predicts poor overall survival in acute myeloid leukaemia. Leukemia 2009; 23: 1029–1038.

    Article  CAS  PubMed  Google Scholar 

  62. Mogi M, Yang J, Lambert JF, Colvin GA, Shiojima I, Skurk C et al. Akt signaling regulates side population cell phenotype via Bcrp1 translocation. J Biol Chem 2003; 278: 39068–39075.

    Article  CAS  PubMed  Google Scholar 

  63. Lagadinou ED, Ziros PG, Tsopra OA, Dimas K, Kokkinou D, Thanopoulou E et al. c-Jun N-terminal kinase activation failure is a new mechanism of anthracycline resistance in acute myeloid leukemia. Leukemia 2008; 22: 1899–1908.

    Article  CAS  PubMed  Google Scholar 

  64. McCubrey JA, Abrams SL, Ligresti G, Misaghian N, Wong EW, Steelman LS et al. Involvement of p53 and Raf/MEK/ERK pathways in hematopoietic drug resistance. Leukemia 2008; 22: 2080–2090.

    Article  CAS  PubMed  Google Scholar 

  65. Brandwein JM, Leber BF, Howson-Jan K, Schimmer AD, Schuh AC, Gupta V et al. A phase I study of tipifarnib combined with conventional induction and consolidation therapy for previously untreated patients with acute myeloid leukemia aged 60 years and over. Leukemia 2009; 23: 631–634.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by grants from Fondazione del Monte di Bologna e Ravenna and Progetti Strategici Università di Bologna EF 2006 to AMM. JAM was supported in part by a grant from the National Institutes of Health (USA) (R01098195).

Author information

Authors and Affiliations

  1. Department of Human Anatomical Sciences, University of Bologna, Bologna, Italy

    A M Martelli, C Evangelisti, F Chiarini & C Grimaldi

  2. IGM-CNR, c/o IOR, Bologna, Italy

    A M Martelli

  3. Department of Health Sciences, University of Cassino, Cassino, Italy

    V Papa & A Cappellini

  4. Transfusion Center, Policlinico S. Orsola-Malpighi, Bologna, Italy

    P L Tazzari, F Ricci & P Pagliaro

  5. Department of Hematology/Oncology, University of Bologna, Bologna, Italy

    G Martinelli & E Ottaviani

  6. Interdisziplin,

    S Horn

  7. ä,

    S Horn

  8. re Klinik und Poliklinik f,

    S Horn

  9. ü,

    S Horn

  10. Forschungsabteilung Zell- und Gentherapie, r Stammzelltransplantation, University of Hamburg, Hamburg, Germany

    S Horn

  11. Division of Hematology and Oncology, Department of Medicine, University of Goettingen, Goettingen, Germany

    J Bäsecke

  12. Department of Internal Medicine III, Hospital of the University of Munich, Munich, Germany

    L H Lindner

  13. Max Planck Institute for Biophysical Chemistry, Goettingen, Germany

    H Eibl

  14. Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC, USA

    J A McCubrey

Authors
  1. A M Martelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. V Papa
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. P L Tazzari
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. F Ricci
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. C Evangelisti
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. F Chiarini
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. C Grimaldi
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. A Cappellini
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. G Martinelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. E Ottaviani
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. P Pagliaro
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. S Horn
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. J Bäsecke
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. L H Lindner
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. H Eibl
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. J A McCubrey
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A M Martelli.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Additional information

Supplementary Information accompanies the paper on the Leukemia website

Supplementary information

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Martelli, A., Papa, V., Tazzari, P. et al. Erucylphosphohomocholine, the first intravenously applicable alkylphosphocholine, is cytotoxic to acute myelogenous leukemia cells through JNK- and PP2A-dependent mechanisms. Leukemia 24, 687–698 (2010). https://doi.org/10.1038/leu.2010.32

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/leu.2010.32

Keywords

  • MEK/ERK signaling
  • PP2A
  • apoptosis
  • caspases
  • leukemia-initiating cells

This article is cited by

Search

Advanced search

Quick links